The overall objective of this research program over the proposed grant period is to devise an efficient synthetic strategy for construction, in chiral form, of various members of the architecturally novel class of tremorgenic alkaloids derived from the ergot fungus, claviceps paspali and related species. Initial synthetic targets include: paspaline (1); paspalicine (2); paspalinine (3); and paxilline (4). Members of this class of tremorgens have been implicated in a wide variety of neurologic disorders, both in laboratory animals and in livestock; examples include Dallisgrass poisoning (the so called paspalin staggers) and ryegrass staggers. Symptoms are characterized by sustained tremors, especially upon voluntary initiation of movements and are accompanied by such effects as limb weakness, ataxia and convulsions. At high dose levels death results. These symptoms, particularly intentional tremors, are similar to those found in certain human disorders such as Wilson's Disease and multiple sclerosis, and may result at the molecular level from a common neurochemical mechanism. Subgoals of this research program will be the development of new synthetic methodology, such as the proposed cyclopentenone annulation sequence, which will have potential applicability to a wider range of pharmacological important agents.